Systematic review and network meta-analysis of the efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler in comparison with other long-acting muscarinic antagonist/long-acting ?₂-agonist fixed-dose combinations in COPD.

ABSTRACT:

Background

Dual bronchodilation with a long-acting muscarinic antagonist (LAMA)/long-acting ?₂-agonist (LABA) fixed-dose combination (FDC) is an established treatment strategy for chronic obstructive pulmonary disease (COPD). The relative efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI 18/9.6??g) in patients with moderate-to-very severe COPD, compared with other licensed LAMA/LABA FDCs, was investigated using an integrated Bayesian network meta-analysis (NMA).

Methods

A systematic literature review and subsequent screening process identified randomized controlled trials of ?10?weeks' duration that enrolled patients aged ?40?years with moderate-to-very severe COPD and included at least one LAMA/LABA FDC or open LAMA?+?LABA treatment arm. NMAs were conducted for outcomes including change from baseline in forced expiratory volume in 1?s (FEV₁), St George's Respiratory Questionnaire (SGRQ), and transition dyspnea index (TDI) parameters, annualized rate of exacerbations, use of rescue medication, adverse events, and all-cause withdrawals. Meta-regression and sensitivity analyses accounted for heterogeneity across studies.

Results

In total, 29 studies including 34,617 patients contributed to the NMA for efficacy or safety outcomes at week 24 or exacerbations. For all LAMA/LABA FDCs with data available, significantly greater improvements in FEV₁ [trough, peak, and area under the curve (AUC)_0-4], SGRQ total score and TDI focal score at week 24, and annualized rate of moderate-to-severe exacerbations, were observed versus placebo. Where indirect comparisons were possible, differences between GFF MDI and other LAMA/LABA FDCs were small relative to established margins of clinical relevance, and not statistically significant. The safety and tolerability profile of GFF MDI was consistent with other LAMA/LABA FDCs and placebo. The results of the meta-regression were generally similar to the base case.

Conclusions

GFF MDI demonstrated comparable efficacy and safety outcomes to other LAMA/LABA FDCs. Personalization of treatment choice within the class on the basis of other factors such as patient preference may be appropriate.

SUBMITTER: Siddiqui MK 

PROVIDER: S-EPMC6928544 | biostudies-literature | 2019 Jan-Dec

REPOSITORIES: biostudies-literature